Identification of antisense RNA transcripts from a human DNA topoisomerase I pseudogene.

Eukaryotic topoisomerase I (TOP1), a DNA unwinding enzyme, plays an essential role in several cellular functions; however, regulation of TOP1 activity remains unknown. In an effort to identify potential regulators of TOP1 activity, the transcriptional activity of a TOP1 pseudogene in chromosome 1 was studied. By using primers unique to the TOP1 pseudogene, strand-specific polymerase chain reaction analysis of HeLa RNA amplified products from at least two transcripts oriented in the antisense direction of TOP1 mRNA. In one case, polymerase chain reaction and Northern blot analysis found a 0.7-kilobase antisense transcript. Upon estimation of 5' and 3' boundaries, a 497 base stretch of homology with the TOP1 mRNA was found. While the function of these TOP1 antisense transcripts remains unknown, recent studies of naturally occurring antisense RNA have demonstrated several potential regulatory roles. The production of antisense transcripts from a TOP1 pseudogene was the first example of a naturally occurring antisense RNA transcript produced from a pseudogene.

[1]  R. Sternglanz,et al.  Transcription-dependent DNA supercoiling in yeast DNA topoisomerase mutants , 1988, Cell.

[2]  J. Battey,et al.  N-myc mRNA forms an RNA-RNA duplex with endogenous antisense transcripts , 1990, Molecular and cellular biology.

[3]  R. Simons,et al.  Naturally occurring antisense RNA control--a brief review. , 1988, Gene.

[4]  W. Earnshaw,et al.  cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Sapp,et al.  Molecular structures of two human DNA topoisomerase I retrosequences. , 1990, Gene.

[6]  Y. Cheng,et al.  Characterization of the 3' region of the human DNA topoisomerase I gene. , 1989, Cancer research.

[7]  E. Vanin,et al.  Processed pseudogenes: characteristics and evolution. , 1985, Annual review of genetics.

[8]  M. Botchan,et al.  Association of crossover points with topoisomerase I cleavage sites: a model for nonhomologous recombination. , 1985, Science.

[9]  R. Hertzberg,et al.  Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. , 1985, The Journal of biological chemistry.

[10]  J. Wang,et al.  Human DNA topoisomerase I is encoded by a single-copy gene that maps to chromosome region 20q12-13.2. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[12]  R. Knippers,et al.  Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks , 1988, Molecular and cellular biology.

[13]  L. Liu,et al.  Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. , 1988, Cancer research.

[14]  A. Richter,et al.  Expression of the type I DNA topoisomerase gene in adenovirus-5 infected human cells. , 1990, Nucleic acids research.

[15]  M. Inouye.  Antisense RNA: its functions and applications in gene regulation--a review. , 1988, Gene.

[16]  E. Beutler,et al.  High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease. , 1990, The Journal of clinical investigation.

[17]  J. Wang.  Recent studies of DNA topoisomerases. , 1987, Biochimica et biophysica acta.

[18]  P. Seeburg,et al.  The structure of eight distinct cloned human leukocyte interferon cDNAs , 1981, Nature.

[19]  M. Kirschner,et al.  An antisense mRNA directs the covalent modification of the transcript encoding fibroblast growth factor in Xenopus oocytes , 1989, Cell.

[20]  M. Dolivo,et al.  Post‐transcriptional events are responsible for low expression of myelin basic protein in myelin deficient mice: role of natural antisense RNA. , 1990, The EMBO journal.

[21]  A. Richter,et al.  Expression of the topoisomerase I gene in serum stimulated human fibroblasts. , 1990, Biochimica et biophysica acta.